Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.

Autor: Helseth AR; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA. nicole.calakos@duke.edu., Hernandez-Martinez R; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA. nicole.calakos@duke.edu., Hall VL; Department of Neurobiology, Duke University Medical Center, Durham, NC 27715, USA., Oliver ML; Department of Cell Biology, Duke University Medical Center, Durham, NC 27715, USA., Turner BD; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA., Caffall ZF; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA., Rittiner JE; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA., Shipman MK; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA., King CS; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA., Gradinaru V; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA., Gerfen C; Section on Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892, USA., Costa-Mattioli M; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA., Calakos N; Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA. nicole.calakos@duke.edu.; Department of Neurobiology, Duke University Medical Center, Durham, NC 27715, USA.; Department of Cell Biology, Duke University Medical Center, Durham, NC 27715, USA.; Duke Institute for Brain Sciences, Duke University, Durham, NC 27715, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Apr 23; Vol. 372 (6540).
DOI: 10.1126/science.abe1931
Abstrakt: The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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